Clinical decisions require timely availability of holistic patient health information including clinical, demographic, behavioral, and socioeconomic risk factors. Health information exchanges (HIEs) help bridge the technical and organizational divides between disparate Electronic health records (EHR) systems and facilitate the sharing of health information between providers and between patients and providers through collaborative governance, secure protocols, and interoperable standards. HIEs come in many varieties and can be highly complex, both technically and organizationally. This conceptual paper adopts a system of systems (SoS) framework from the systems engineering discipline to analyze and break down the complexity of HIEs. The mnemonic nature of the five characteristics of the Boardman and Sauser SoS Model (A for Autonomy, B for Belonging, C for Connectivity, D for Diversity, and E for Emergence) makes it easier to understand the intricacy of HIEs and helps remove the barriers to effective use of HIEs for care coordination, patient safety, and patient-centered care quality.